OBJECTIVES OBJECTIVES 1. To understand how blood glucose levels are regulated by hormones, especially epinephrine, glucagon, and insulin. 2. To examine metabolic consequences of loss of glucose homeostasis. 3. To understand how glucose is synthesized from other substrates, and which substrates can be used for this purpose. 4. To understand how glycolysis and gluconeogenesis are coordinately regulated so as to avoid futile cycles in the cell.

● Gluconeogenesis is the term used to include all mechanisms and pathways responsible for converting non-carbohydrates to glucose or glycogen. ● The major substrates are the glucogenic amino acids; lactate; glycerol; and propionate. ● Gluconeogenesis occurs in the liver and kidney, the only organs with a full complement of the necessary enzymes.

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Biomedical Importance Biomedical Importance ● The biosynthesis of glucose is an absolute necessity of all mammals, because the brain and nervous system, as well as erythrocytes, testes, renal medulla, and embryonic tissue, require glucose from the blood as their sole or major fuel source. ● The human brain alone requires 120 g of glucose each day. Below a critical blood glucose concentration (normal = 65-110 mg/dL or 3.6-6 mM), brain dysfunction can occur which can lead to coma and death. ● Even when fat may be supplying most of the caloric requirements of an organism, there is always a certain basal requirement for glucose e.g. in skeletal muscle under anaerobic conditions. ● Glucose is precursor of lactose in the mammary gland. ● Gluconeogenic mechanisms are used to clear lactate (from muscle and erythrocytes) and glycerol (adipose tissue) from blood.

Gluconeogenesis vs. Glycolysis Gluconeogenesis vs. Glycolysis ● Thermodynamic barriers prevent a simple reversal of glycolysis in conversion of pyruvate to glucose. ● 7 of 10 reactions of gluconeogenesis are the reverse of

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